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INTERIM HEALTH TECHNOLOGIES ASSESSMENT (HTA) IN ROMANIA. A proposal for a better transition to full HTA
Marian Sorin PAVELIU MD, PhD, assoc. prof. At Titu Maiorescu University, Bucharest Romania, dept. of Pharmacology
For more than a decade health technologies assessment (HTA) introduction in Romania was a recommendation made by various consultants engaged in reforming the Romanian health system. In the last 6 years no new products have been accepted on the reimbursement drug list. In the spring 2013 Ministry of Health issued a new methodology for assessing pharmaceutical products, considered to be a form of interim HTA, and to start the use of similar methodologies to the ones used in most European countries. We deem that this process is a stagnation or even a step backward in introducing full health technology assessment and we listed some of the pressing issues. Given these shortcomings we presented a proposal for a methodology inspired by some of the foreign consultants' reports, amended and completed with new recommendations, with the purpose of ensuring the transition from 2015 to full HTA, aiming ultimately for an increase in cost-effectiveness of the health system and, eventually an increase in equity.

1. INTRODUCTION

Health Technology Assessment (HTA) is a multidisciplinary process that aims to use multiple approaches and techniques in order to provide health policy makers with a broad perspective on products or services designed to have access to public funding. The assessment takes into account efficacy, safety, efficiency, social, legal and ethical aspects, Keywords: HTA - Health Technology Assessment, health policy, health etc. A large range of medical interventions benefit from HTA, such as: the introduction of a new drug reform, economic evaluation or a biological product, an intervention like organ transplant, a practice protocol, finally allowing a compariOrder). This methodology of "interim HTA" - was inson of them. [1] tended as a form of transition to a future evaluation allowing a revision of the reimbursement drug list starting immediately. Although it should have been a step forward in 2. PREVIOUS EFFORTS AND RECOMMENDAintroducing HTA, the new procedure does not approach TIONS FOR HTA INTRODUCTION IN ROMANIA the minimum requirements of an economic evaluation; its Introduction of HTA in Romania is a goal and effort to effects represent just another version of the previous legal start this process is dating back for more than a decade. framework. The need of using HTA in health policy decisions in RoFrom the standpoint of innovative medicines, the main mania was highlighted in 1992, following a study funded evaluation criteria are: the result of the evaluation in by the World Bank. [2] [3] Even at the time, the use of France and the UK (1 point each), reimbursement status in HTA was a well established process in many EU countries. the rest of the EU countries (up to 2 points), the relative For example, Spain has appealed to HTA specialists since effectiveness (max. 2 points), the relative safety (max. 2 1988, and in 1991 was created the HTA Office in the Minpoints) and the results reported by patients (max. 2 points). istry of Health of Catalonia [4] National Institute for Obtaining a minimum of 6 points draws the inclusion on Health and Care Excellance (NICE), the best known instithe reimbursement drug list. tution of this type in the world, was founded in the UK in Marketing authorizations holders must provide further 1999 [5]. information regarding (but without influencing the accepThe following will highlight a proposal for a methodology tance process): which takes into account a modified version of several Choosing a comparator drug; recommendations made for Romania by foreign consultants and supplemented with measures to minimize the bias Analysis of the budgetary impact, and and direct involvement of officials in the interim evalua The cost-effectiveness, as shown in published studies. [6] tion of health technology. 3. A CRITICAL ANALYSIS OF THE CURRENT LEGAL FRAMEWORK ON ACCESS TO THE REIMBURSEMENT DRUG LIST After a period of six years, the authorities have not granted access to the list of subsidized drugs due to substantial arrears toward drug manufacturers. In June 2013 the Ministry of Health (MoH) issued Order 724 (referred to as Some of the drawbacks of the Order include:

The absence of a time table for the transition from a interim to a full HTA;

The scorecard used, decisive for accepting the compensation status, is not enough influenced by the reimbursement status in other jurisdictions,

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In a previous issue of the journal [8], Radu and Pana raised the idea that different evaluation agencies usually come to the same conclusions - giving the example of NICE (UK) and the SMC (Scotland) evaluations, the last ones methodology being more pragmatic and using far less resources; this could back up the idea for the use of evaluation from other countries in the case of Romania or at least the most simplified methodology possible. The extrapolation of study results without regard to the specifics of Romania is completely erroneous and misleading for the uninformed reader. There are supporters of the idea that the HTA process may be carried out centrally, at an EU level, as the actual centralized licensing for a new drug. Article 15 of the Cross-border Patients Rights Directive (2011/24/EU) includes cooperation on Health Technology Assessment as relevant area for cooperation between Member States in the field of public health and sets up a voluntary network connecting national authorities and bodies responsible for HTA. In my opinion this is an important step to a harmonization of HTA around UE, but the process will be long and difficult.[9] The actual procedure requires mentioning the costeffectiveness indicator (incremental cost-effectiveness ratios ICER) as it was calculated using data from advanced economic countries. Several studies have shown that the transfer of conclusions from studies conducted in jurisdictions of greater economic power than the target countries is unlikely to be suitable and a proper adaptation of these conclusions and results should be made. [10] Romania does not meet most of the criteria for the transferability of cost-effectiveness studies and budget impact analysis, and consequently, new studies should be performed, using our country specific data. 4. PROPOSALS FOR THE TRANSITION TO A FULL HTA IN ROMANIA In order to properly defining the current assessment as interim the first step is to determine when and how a full assessment of new technologies will be carried out. In our opinion an interval of 6 to 9 months is sufficient for Romania to have a stabilized method of assessment and a sufficient number of officials trained in HTA to verify the validity of the assessments provided by the manufacturers. Our proposal is that the new drugs, which meet the minimum criteria to be included in the evaluation process, should be accepted for financing under special conditions for a period of 12 mothns with the possibility to extend for another 6 months. In the first 12 months all the necessary data will be gathered regarding the clinical efficacy, epidemiology and healthcare structure specific for Romania. In the last 6 months of funding the producers will have to complete their studies and submit the results to the authorities for a final reimbursement decision, without patients already receiving treatment in question to be forced to stop their treatment. 5

comparable to the economic status of Romania; the points awarded for efficacy and safety profile can be viewed as formal given that most products have already passed through the filter of the European Medicines Agency. It has qualified the the drugs in question as being equal or greater to the the comparison treatment in terms of aforementioned criteria! Most of candidate products generally receive at least 6 points and lead to automatic compensation!; Budgetary Impact Analysis serves only an informative purpose; it is self-assessed and does not bind in any way the manufacturer for undervaluation. This analysis could have been one of the main grounds for negotiating the future sales of the reimbursed drug; The procedure does not indicate how the additional costs will be covered and what will be the impact on the pharmaceuticals budget; a welcomed measure would have been to allocate a designated budget for innovative medicines. In Romania over-spending of the reimbursed drugs budget is supported entirely by the drug manufacturers. Today drug producers have to payback to National Health Insurance House (NHIH) around 10% of their income. An increase by 10-15% in the market will force the manufacturers to pay in addition to VAT, income tax, etc,. almost 25% of their turnover, which is unlikely to be accepted. The reimbursement of new technologies will require a substantive change to the payback system which will rise the risk that this will leave behind a financial imbalance which will be difficult to manage for the NHIH; The Order fails to provide any negotiation mechanism of the price after the new drugs will be accepted on the reimbursement list. Once the assessment is concluded, the third party payer, NHIH, will be obligated to include the new products on the reimbursed list without having any legal means of negotiating the quantity and/or price of the products; There is no procedure in place that can reevaluate over the course of time the admission decision on the reimbursement list; The order does not provide evaluation of the products already reimbursed, some of which have questionable cost and effectiveness. At least theoretically, in the absence of any barrier, the Order allows drugs considered to be too expensive or even not cost-effective in some economically advanced countries to access the list of subsidized drugs in Romania! In 2011, 30 of the top 50 drugs ranked by spending were rated by NICE international consultants as being too expensive, considering the purchasing power of our country; [7] We believe that the current methodology marks a stagnation which will have negative consequences. It is not based on a budget impact analysis which can lead to malfunctions and arrears and thus waste the opportunity to make a full assessment of more than 150 molecules and new indications.

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The transition period will be split into a series of Table 1 - Special evaluation criteria for candidate pharmaceutical phases, some of them already suggested by inde- products [after Seiter, modified] [12] pendent experts who advised the Romanian GovernCoding Special criteria ment. [7] The disease has a high im- 2= It affects Public health portance for public health in 1= It affects only certain individuals Phase I cessation of ineligible products that are Romania 0= other situation ineligible (Note = the most of products them will get Given that Romania is among the EU's poorest 1 pct) countries [11] - borrowing experience from some of The new treatment is not 2= Is not more expensive the richest countries, like the UK or France, is inade- more expensive than current 1=Is in a coplarable range (0-10% more quate. We believe that, for the moment, and at least standard treatments in Ro- than current therapy) until the development of its own expertise, Romania mania 0= Is more expensive than current therapy should rely on precedents set in five countries, with (Note = the most of products will receive 0 pct) an close GDP / capita according to Eurostat namely Slovakia, Hungary, Estonia, Lithuania, Bul- The new treatment has 2= Has proven and semnificative advangaria. tages in clinical trials. clear clinical advantages 1= Is a mee too drug. A. Seiter proposed in his Pharmaceutical Sector over older treatments in a Analysis Report [12] a scorecard considering juris- way that patients wellbeing, 0= Has no proven advantages. (Note = most of products will receive 2 dictions with close economic power superior to Ro- functioning or life expectancy are improved in a sig- pcts) mania. Each product would receive 2 points for their nificant and relevant way status recorded unrestricted 1 pt - pt product registered with restrictions (limited number of patients, It is possible to deliver the 2= Similar medical practice in Romania stated, price-volume, etc) and 0 points for unregis- new treatment according to 1= Is requesting supplimentary costs to good practice in the Roma- monitor the treatment tered products. 0 = there are not similar conditions comnian health system For a product to qualify should accumulate at least 5 (diagnostic tools available, pare to those where the drug was tested points obtained from the comparison with the control instruments avail(Note = the most of products will receive reference countries. A product reimbused with able etc.) 2 pcts) restrictions in all 5 countries will accumulate 5 points. The same number of points can be obtained Out-of-label use can be con- 2= Out-of- label use can be prevented 1= Out-of- label use can be prevented if if the two countries have unrestricted reimbursed the tained easily additional preventive measures will be product and one reimbused with restrictions. enforced In conclusion, if comparable countries with 0= Out-of- label use cant be prevented Romania were given 2-6 years and have not decided (Note = the most of product will get 2 for listing, provided that all applicable pcts) comprehensive economic assessment procedures were used it is not appropriate for Romania to proceed Priority will be granted to studies using as a comparator otherwise. products already reimbursed in Romania. From these data we can extract the number of QALY gain by introducing Afterwards products will be evaluated using specific critenew technology compared to standard technology, inforria as follows (see table 1): mation that will be used in the next step. From the special criteria the eligible items should accumulate at least 7 points. In an extreme scenario, a product would be intended only for the individual treatments Phase III Setting budget and number of patient to be (1pct), have a higher price than current therapy (0 pts), treated in the transitional state till full HTA have clear advantages over current treatment (2 points), could be applied in Romania (2 points) and should be pos- III.1 Budget setting for each product sible to prevent off-label administration (2 points). For each tranche of innovative products that will enter into transitional reimbursement phase the Government / ParliaPhase II Checking the provision of relevant informament will allocate a budget to them according to economic tion of benefits compared with current standard of opportunities. care. Each product will be assigned a budget in accordance with The the manufacturers submitted application will include the number of QALYs generated (eg. Let assume the apall the relevant data on cost-effectiveness of the product proved budget of 200 million Euros - and a total generated indicating studies that were submitted to the authorities in of 50 QALY per patient gathered from all products 6 other countries and those who came later.

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Phase V-a Reassesement of data at every 5 years from acceptance on the reimbursment list Given the changes in time of costs and prices of various procedures and drugs entering the market, and the occurrence of new technologies, etc, periodically a reassessment of the initial decisions is justified. Reassessment of the initial evaluation will be based on the economic models originally submitted or using new studies that could be carried out every 3-5 years.

included; if a product that will generate 0.5 QALY will receive a budget of 2 million for the transitional period of 18 months of assessment). - III.2 Price setting for transitional state For the transitional state the contract the price shall be determined as follows (de facto HTA) [7]: Prices in Romania = Price in country A X

PPP adjusted acording GDP per capita in Romania

PPP-adjusted according GDP per capita in the country of reference Where A - is one of the countries chosen by the manufacturer of the 5 mentioned above provided that the product has been fully reimbursed or with restrictions, PPP is purchasing power parity, GDP is Gross Domestic Product. This formula of calculation will be used only till 2015, staring when producers will have to provide pharmacoeconomic evaluation performed entirely on their expenses. - III.3. - Determining the number of patients and clinical centers that will be designated for administering a product in the transitional state To achieve the purpose of the existence of a transitional period - obtaining Romania specific data on the effectiveness and efficiency of the product a Phase IV clinical trial will be run - meeting all the requirements laid down in legislation, with the approval of the National Agency for Medicines and Medical Devices. The manufacturer will be responsible for bearing the costs of monitoring - including those related to implementation of a disease or patients registry. the number of patients will be determined by dividing the allocated budget to each product to the treatment transiently cost. Phase IV full HTA In the next 6 months after the first 12 months, the manufacturer will be able to provide to authorities all the necessary data used to perform the actual HTA, mainly for costeffective studes using comparator reimbursed in Romania and a full budget impact analysis. The collected data will enable the achievement of other recommendations of various experts who have advised Romania signing costvolume-outcome contracts or other forms of risk-sharing contracts from more than 100 different types currently in use around the world. Then authorities may decide unrestricted compensation of the product according to clinical experience and budgetary impact, limited compensation or reject of the reimbursment request.

ISCUSSION AND CONCLUSIONS

This methodology would be a transition period, and since 2015 all products will aspire to public financing will opt for the use it or providing their own funded studies using Romania data. NHIH may demand of the manufacturers of the first 150-200 medicinal products (ranked according cost per year / course) already reimbursed to produce scientific evidence for a full HTA. During this evaluation a temporary price could be imposed, for exemple low enough to cover the treatment of the patients existing on the waiting list. The same principles, with minor modifications, could be applied to any other medical technologies that are currently publicly funded, such as devices, vaccines, dialysis, etc. NHIH and/or MH must publish guidelines for emergency budgetary impact assessment studies and for studies of cost-effectiveness and to fund a clinical trial for calibration of utility values specific to Romania. Agreeing on the the World Health Organization recommendation for a threshold for ICER or Country specific thresholds. Integrated Information System (SIUI) should be adjusted to allow even before the introduction of electronic patient safety modules that act as patient registries or disease used to assess new technologies under evaluation. Products in transitional period of assessment should not be taken into account in computing the clawback tax. In 12 months the Ministry of Health should complete training of officers who will be responsible for HTA. a year ago MS started a training process, a total of 15 physicians completing courses through a project funded by the World Bank specialists only one of them beeing used in the current evaluation system. 7

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The prospect of implementing a full system of HTA in 2015 must be done simultaneously with the enactment of a series of legislative changes such as the introduction of new levels of compensation, the change of the claw-back tax and the introduction of cost-volume contracts, cost -volume-outcome and even switching to contracts where payment to be made only for pa-

tients who achieve the outcomes (pay for performance) [13].

Such a system would also reduce the interim evaluation bias and suspected corruption, imposing maximum transparency, aimeing for a higher standard as is the case in all advanced countries.

References 1. European Commission. Public Health http://ec.europa.eu/health/technology_assessment/policy/ visited in Aug 2013; 2. MOGA, C., CORABIAN, P., HARSTALL, C., et al., -Developing health technology assessment n Romnia, Eurohealth, 9:30-34., 2003; 3. CORABIAN, P., HAILEY, D., HARSTALL, C. JUZWISHIN, D., MOGA, C., -Mentoring a developing health technology assessment initiative n Romnia: an example for countries with limited experience of assessing health technology, Int J Technol Assess Health Care, 2005 Fall; 21(4):522-5., 2005; 4. SAMPIETRO-COLOM, L., ASUA, J., BRIONES, E., GOL, J.; AUNETS Group, - History of health technology assessment: Spain. Int J Technol Assess Health Care. 2009 Jul;25 Suppl 1:163-73., 2009; 5. NIEMIETZ, K., PUGATCH, M.P. , -Health Technology Assessment in the UK and Germany www.stockholm-network.org/downloads/publications/HTA3_2.pdf descarcat in august 2013; http://

6. Order no. 724/2013 for the approval of medical technology assessment criteria, documentation to be submitted by applicants, the methodological tools used in the assessment and evaluation methodology on the in expanding indications of medicines, inclusion or non-inclusion of common international names drug list benefiting policyholders on prescription, with or without personal contribution. Published n Romanian Official Gazette no. 339 from 10.06.2013; 7. LOPERT, R., et al., -Applying rapid de-facto HTA in resource-limited settings: Experience from Romania. Health Policy (2013), http://dx.doi.org/10.1016/j.healthpol.2013.07.019; 2013; 8. RADU, C.P., PAN, B., -Key aspects regarding the introduction of health technology assessment in Romania, Management in Health, vol 17, no 2 (2013); 9. Directive 2011/24/eu of the european parliament and of the council of 9 march 2011 on the application of patients rights in cross-border healthcare http://eur-lex.europa.eu/LexUriServ/LexUriServ.do? uri=OJ:L:2011:088:0045:0065:EN:PDF; 2011; 10. WELTE, R., FEENSTRA, T., JAGER, H., LEIDL, R., -A decision chart for assessing and improving the transferability of economic evaluation results between countries. Pharmacoeconomics. 2004;22(13):857-76; 2004; 11. Eurostat: GDP per capita, consumption per capita and price level indices http://epp.eurostat.ec.europa.eu/ statistics_explained/index.php/GDP_per_capita,_consumption_per_capita_and_price_level_indices descarcat in august 2013; 12. SEITER, A., -Romania: Pharmaceutical Sector Analysis, http://apps.who.int/medicinedocs/documents/s16762e/ s16762e.pdf descarcat n august 2013; 13. GARBER, A.M., McCLELLAN, M.B., -Satisfaction guaranteed--"payment by results" for biologic agents. N Engl J Med. 2007 Oct 18;357(16):1575-7; 2007.